chr17-7024229-C-G

Position:

• chr17-7024229-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_181844.4(BCL6B):​c.326C>G​(p.Pro109Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,570 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: BCL6B NM_181844.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.976

Genes affected

BCL6B (HGNC:1002): (BCL6B transcription repressor) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in several processes, including regulation of gene expression; regulation of inflammatory response; and type 2 immune response. Predicted to be located in nucleus. Predicted to be active in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

BCL6B (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25954056).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BCL6B	NM_181844.4	c.326C>G	p.Pro109Arg	missense_variant	3/9	ENST00000293805.10	NP_862827.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BCL6B	ENST00000293805.10	c.326C>G	p.Pro109Arg	missense_variant	3/9	1	NM_181844.4	ENSP00000293805.5
BCL6B	ENST00000576705.1	c.326C>G	p.Pro109Arg	missense_variant	3/3	4		ENSP00000460071.1
BCL6B	ENST00000573503.1	c.326C>G	p.Pro109Arg	missense_variant	2/2	2		ENSP00000460282.1
BCL6B	ENST00000572216.1	n.234C>G		non_coding_transcript_exon_variant	3/4	4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461570 Hom.: 0 Cov.: 38 AF XY: 0.00 AC XY: 0 AN XY: 727096

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 22, 2024

The c.326C>G (p.P109R) alteration is located in exon 3 (coding exon 2) of the BCL6B gene. This alteration results from a C to G substitution at nucleotide position 326, causing the proline (P) at amino acid position 109 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Benign	-0.016	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T;.;.
Eigen	Uncertain	0.21
Eigen_PC	Benign	0.16
FATHMM_MKL	Benign	0.40	N
LIST_S2	Benign	0.71	T;T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.26	T;T;T
MetaSVM	Uncertain	-0.18	T
MutationAssessor	Benign	0.050	N;.;.
PrimateAI	Uncertain	0.68	T
PROVEAN	Benign	-0.46	N;.;.
REVEL	Benign	0.26
Sift	Benign	0.41	T;.;.
Sift4G	Uncertain	0.030	D;T;T
Polyphen		1.0	D;.;.
Vest4		0.33
MutPred		0.56		Gain of methylation at P109 (P = 0.0087);Gain of methylation at P109 (P = 0.0087);Gain of methylation at P109 (P = 0.0087);
MVP		0.88
MPC		0.80
ClinPred		0.62	D
GERP RS		5.2
Varity_R		0.17
gMVP		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1321380552; hg19: chr17-6927548;